Abstract
Sirtuins (SIRTs) overexpression serves as a potential therapeutic target for TNBC because it is associated with bioactivities of cancer stem cells (CSCs), resistance to chemotherapy, and metastasis. Irrespective of the availability of synthetic SIRT inhibitors, new SIRT inhibitors with enhanced potency and lesser side effects serve as current unmet needs. Therefore, bioactive dietary compounds; kaempferol (KMP) and apigenin (API) were investigated for their anti-SIRTs potential. We observed KMP and API inhibits cellular proliferation by DNA damage and S-phase cell cycle arrest in TNBC Cells. They also suppress stemness properties in TNBCs as observed in experiments of mammosphere formation and clonogenic potential. Our mechanistic approach indicated that KMP and API inhibited SIRT3 and SIRT6 proteins, as evidenced by our in silico and in vitro experiment. Collectively, our studies suggest that KMP and API are promising candidates to be further developed as sirtuin modulators against TNBCs.
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